CN1117558C - Compositions containing an antifungal and a sulfur compound - Google Patents

Abstract

The invention relates to compositions such as body and hair cleansing products, in particular shampoos, comprising one or more fungal ergosterol biosynthesis inhibiting antifungals as a first active ingredient and a pyrithione salt as a second active ingredient.

Description

The composition that contains fungicide and sulphur compound

The present invention relates to for example composition of body and function and hair cleaning products, particularly relate to shampoo, its comprise one or more can the Antifungi ergosterols biosynthetic fungicide as the first active component, pyrithione salt as the known body and function of the second active component and prior art or hair cleaning products component as carrier.

                       Background of invention

Known medicated shampoo is for example with the commercially available ketoconazole shampoo of 2% preparation, and it shows useful effect to seborrhea after topical application. The people such as Rosenberg are at US-4,569, disclose ketoconazole in 935 and have been used for topical therapeutic psoriasis and seborrhea. At US-5, disclose the ketoconazole shampoo in 456,851 and had preferably cosmetic properties and for example bubble and the property nursed one's health, they have acceptable stability to degraded, so that they can be formulated into to contain and are lower than 2% active component. Known by WO-93/18743, except having fungicidal action, also have the effect of regulation of skin grease according to Lu Biou (elubiol) shampoo. The preparation of some anti-dandruffs contains coal tar, selenium sulfide or pyrithione salt, and for example pyrithione zinc or sodium are as active component. The mixture that WO-96/29045 usually discloses this cytotoxin reagent and fungicide is used for the treatment of the brawny tetter dermatitis; Concrete disclosed is to mix to use the uncertain solution of composition that comprises the uncertain composition of 1.8% coal tar oil composition and comprise 2% ketoconazole. WO-96/29983 discloses gentle aqueous detergent compositions, it comprises about 4% to about 12% (weight) anion surfactant, a kind of amphoteric surfactant, its content accounts for 0.75 part (weight) of said anion surfactant weight at least, and in 11 kinds of listed therapeutic agents one or more. Also have other to contain the antidandruff shampoos of selenium sulfide, when oral or when being applied to large-area skin, it is poisonous.

The shampoo that comprises anti-dandruff reagent of prior art is designed to reach optimum balance between effect and tolerance; The concentration of active component in medicated shampoo is so that user as much as possible is effectively treated and makes the least possible user to suffer illeffects. However, still have a considerable amount of patients not benefit from the shampoo that uses prior art, because they do not reply this treatment or become more serious, because they can not tolerate the treatment that this employing specific medication shampoo carries out.

Patient's quantity that the specific medication shampoo is not replied is very high (ketoconazole as many as 30%; Selenium sulfide as many as 40%). Therefore, new shampoo is adopted in strong request, and its patient for the vast scale quantity of using this new shampoo provides effective anti-dandruff treatment; Namely compare with the shampoo of prior art, nonresponder's still less new shampoo is arranged.

On the other hand, there are the patient of dandruff or seborrhea and the official of approval medicated shampoo to require all the more this shampoo should satisfy stricter standard. In these standards, the most important thing is: do not exist because the further aggravation of the state of an illness that this treatment causes; The impact of possible side effect is minimum; There is not the further increase of the degree of following symptom: for example stimulation, itch and decortication (adhering to and two kinds of loose decortications); The cosmetics that improve are acceptable; Good cleaning performance does not particularly exist bad smell or foul smell, clothes is polluted or makes dirty, and comprehensively conditioning (wet and do binding property). Dandruff or seborrhea are usually supervened more or excessive oil or sebum, can further improve significantly treatment to dandruff to its composition with beneficial effect.

So far, in order to reach above urgent requirement, most of effort all spends in the base-material of again preparing shampoo. Yet, also need to improve the tolerance/acceptability of medicated shampoo, namely need new shampoo, use the patient of the vast scale quantity of this new shampoo can tolerate better them.

                       Invention is described

The present invention relates to for example composition of body and function and hair cleaning products, shampoo particularly, it comprises, for one or more of main composition or composition can the Antifungi ergosterols biosynthetic fungicide as the first active component, pyrithione salt as the known body and function of the second active component and prior art and hair cleaning products component as carrier. In the following description, use shampoo as embodiment the present invention to be described, but it will be apparent to one skilled in the art that this composition of the present invention can be by purposes application of the present invention, it also can be used as other body and function and hair cleaning products.

Have two kinds not the mixture of the anti-dandruff reagent of same-action have two kinds of special advantages than the shampoo that prior art contains single active component. The first, the ratio quantity that shampoo of the present invention is produced the patient that dandruff or seborrhea are arranged who replys increases. The second, some combinations can act synergistically, and its result can reduce the concentration of one or both dissimilar components, increases thus tolerance. Next coming in order are discussed every class component.

The biosynthetic fungicide of energy Antifungi ergosterol is pyrroles, allylamine or their mixture preferably. Preferred pyrroles is selected from ketoconazole, econazole, elubiol, MCZ, Itraconazole, Fluconazole and their mixture. Preferred allylamine is selected from Terbinafine, neftifine and their mixture. Pyrroles's compound: ketoconazole, econazole and elubiol are most preferred, because they can destroy the common flora on the common flora, particularly scalp of skin at least. Ketoconazole and elubiol are particularly preferred, because can produce mutual synergy (vide infra) to dermatophyte when they are combined with pyrithione salt. The effective dose of fungicide is about 0.1% to about 2 % (w/w) in the present composition, and preferred about 0.5% to about 1% (w/w) scope. Below be described further, under the lower value of this scope, take possibly special safeguard measure, in order to guarantee that shampoo can be owing to the degraded of fungicide in storage loses its effectiveness. Being higher than indicated concentration can not have to the treatment of the state of an illness any further improvement, and fraud is greater than benefit in a word.

The content of the second active component pyrithione can be about 0.05% to about 2% (w/w), and preferred about 0.3% to about 1% (w/w). Those skilled in the art can recognize easily that the character of pyrithione salt of particular form is influential to this consumption (representing with %w/w). Therefore, the amount of the pyrithione of above-mentioned amount and all following indications is for expression pyrithione zinc [molecular weight=317.7]. Pyrithione zinc and sodium pyrithione are preferred pyrithione salt.

Preferred first and second kinds of active components are with to suppressing dermatophyte, particularly the growth of the bacterial classification relevant with dandruff and seborrhea produces mutual synergistic amount existence, said bacterial classification is the avette fish-scale of chaff shape mould (pityrosporum ovale) (Malessezia (Pityrosporum) ovale, M.furfur), but also have other with such as the relevant bacterial classification such as microsporia, favus of the scalp, pityriasis versicolor for example Epidermophyton, Microsporon, Trichophyton. The ratio of first and second kinds of amount of active ingredients will depend on character and the target bacterial classification of said active component. Particularly, estimate between first and second kinds of active components that (fungicide: part by weight pyrithione) can be at about 5: 1 to about 1: 5, particularly about 2: 1 to about 1: 2 scopes. For example, as mentioned above, ketoconazole and elubiol are when being used in combination with pyrithione salt, particularly when with similar consumption for example weight ratio at about 2: 1 during to about 1: 2 scope, particularly when the weight ratio scope was used in about 1: 1, to dermatophyte, particularly the avette fish-scale of chaff shape mould (pityrosporum ovale) is produced mutually synergy. That these combinations also produce mutually synergy to the pathogenic yeast Candida albicans unexpectedly.

Shampoo of the present invention can comprise other anti-dandruff composition, for example selenium sulfide, Octopirox or Brafen.

Shampoo of the present invention can use the known shampoo base-material of prior art to prepare easily; The known shampoo component of prior art comprises one or more surfactants, blowing agent, be enough to make end article viscosity at room temperature at thickener, anticorrisive agent, the antioxidant of 4000 to 9000mPa.s scopes, be enough to make the pH of shampoo at about 4 acid or alkali or buffers to about 10 scopes. Single component can have two or more functions, for example surfactant and blowing agent, or antioxidant and buffer.

The surfactant that is applicable to shampoo of the present invention can be selected from C_14-16Alkene sulfonic acid sodium, NaLS, lauryl sulfate TEA salt, sodium laureth sulfate, coconut acylamino-propyl group amine oxide, lauryl amine oxide, the amino DEA of lauroyl, AMPHORAM C30, Empigen, coco dimethyl sulfopropyl betaine, cocoyl sodium sarcosinate, Disodium Monooleamido MIPA-Sulfosuccinate, DISODIUM COCO AMIDOMIPA SULFOSUCCINATE, lauryl ether disodium sulfosuccinate, coconut both sexes carboxyl-glycinate, the amino MEA disodium sulfosuccinate of oleoyl, amine glycinate, amine propionate and amine sulfobetaines and their mixture. Can use the mixture of two or more different surfaces activating agents in the preferred shampoo of the present invention, particularly sodium laureth sulfate and cocoyl sodium sarcosinate, or NaLS, sodium laureth sulfate, lauryl sulfate TEA salt and AMPHORAM C30. In shampoo of the present invention, the total amount of surfactant can be about 36% to about 45% (w/w) scope. The weight of preferred amphoteric surfactant is less than 15% (weight) of surfactant total amount.

In above definition and hereinafter, term ' MEA ' expression RCO-NH-CH₂CH ₂The single ethanol amide of-OH, term ' DEA ' expression RCO-N (CH₂CH ₂-OH) ₂Diglycollic amide, ' TEA ' represents triethanol ammonium; Term ' MIPA ' expression RCO-NH-CH₂CHOH-CH ₃Single isopropanol amide; Wherein each RCO group is fatty acid residue, for example C_13-19Alkyl-carbonyl or C_13-19Alkenyl carbonyl.

The blowing agent (foam improver and stabilizing agent) that is applicable in the shampoo of the present invention can be selected from aliphatic acid list and di alkanolamide, comprises coconut monoethanolamide MEA, coconut monoethanolamide DEA, oleamide MEA, oleamide DEA and their mixture. The content of blowing agent can be about 1% to about 10% (w/w), and preferred about 2% to about 6% (w/w), and particularly about 4% to about 5% (w/w) scope. These components generally also have the effect of thickening to preparation.

The anticorrisive agent that is applicable to shampoo of the present invention is the acceptable anticorrisive agent of skin, EDTA four sodium for example, methylparoban, oxybenzene propyl formate, oxybenzene butyl formate, oxybenzene Ethyl formate, imidazolidinyl urea, phenoxetol, quaternary ammonium salt 15, citric acid are preferably with alternative mixture wherein. EDTA four sodium and citric acid also can be used as chelating agent and work.

As at US-5; 456; disclosed in 851; when ketoconazole or any other concentration of fungicide of being used for this respect purposes are when being in the lower value of above-mentioned scope; the careful antioxidant that adds controlled quentity controlled variable comes effectively ketoconazole or other pyrroles of stable existence in shampoo; avoid in the process in 50 ℃ of 13 weeks of accelerated ageing, degrading; described antioxidant is selected from Yoshinox BHT (BHT), butylated hydroxyanisol (BHA), ascorbic acid and NAC, and this senile experiment is considered to predict that product at room temperature stores 2 years performances in the process. Think that effective stability is no more than about 10 % of the loss of active component in storage process. The ratio of having found the most effective BHT or BHA is to about 1% (w/w) scope about 0.01%. Although make the time lengthening of accelerated ageing more than 13 weeks, the BHT of larger proportion or BHA tendency are more effective, can not effectively stablize ketoconazole greater than the ratio of this amount in the accelerated ageing process in 13 weeks, because BHT or BHA itself also will be through degraded. Yet government authorities and medicine and cosmetics industry can clearly realize that all be complete enough through the stability of normal shelf life in the storage life in 2 years at 50 ℃, the stability experiment in 13 weeks at room temperature for the prediction product. Also of equal importance is (that is, to make the possibility of sensitization of skin reduce to minimum) for reasons of safety, BHT or BHA that the needs use is a small amount of as far as possible.

Because it is viscosity slightly that the user of shampoo expects shampoo, therefore usually comprises one or more thickeners in preparation, its viscosity that makes product is at room temperature in 4000 to 9000mPa.s scopes. The thickener that is fit to is carbopol preparation or polycarboxylic acid, for example Carbopol^TM1342, it is at the end of preparation, by adding NaOH or sodium chloride by thickening. Other thickener that is fit to is above-mentioned blowing agent, preferred coconut monoethanolamide MEA.

Shampoo of the present invention also can comprise conditioner, for example polyquaternium-7 or similarly cation quaternary salt polymer, for example polysiloxanes quaternary salt polymer; One or more pearling agents, it is selected from diglycol stearate, Tego-stearate and their mixture; And/or one or more spices and one or more colouring agents.

The pH of shampoo of the present invention can determine with the acceptable acid of skin, alkali and buffer easily. PH can be about 4 to about 10, but preferably about 6.5 to about 8, particularly about 6.9 to about 7.4 scopes.

When at approximately neutral pH (pH6 to 8), some pyrithione salt and some the first active components have limited dissolubility. In order to keep these reagent to be evenly distributed in the shampoo, can add for example Avicel RC-591 of suspending agent^TM(the cellulosic mixture of CMC sodium and crystallite attitude). Therefore yet the solvent of several shampoos itself has sizable suspension character, comprises in shampoo of the present invention that specific suspending agent chooses wantonly fully.

The component of shampoo of the present invention routinely consumption is used, for example: (a) 36%-45% surfactant, (b) 2%-6% blowing agent, (c) 0.1%-2% fungicide, (d) 0.05%-2% pyrithione salt, (e) 0.2%-1.3% thickener, (f) 0.01%-1%BHT or BHA; (g) be enough to stop the final composition degraded in order to be met the anticorrisive agent of the storage period of requirement, (h) obtain pH at acid, alkali or the buffer of required scope, (i) an amount of water adds to 100% (that is, enough water is to reach 100%).

The method that the present invention prepares above-mentioned composition or shampoo can may further comprise the steps:

(a) solution of heating thickener and deionized water,

(b) surfactant, blowing agent and optional pearling agent are mixed with solution (a),

(c) BHT is mixed with solution (b),

(d) fungicide is mixed with solution (c),

(e) pyrithione salt is dispersed in the mixture of (d),

(f) make the slightly cooling of suspension of (e), with them with anticorrisive agent, mix for being thickened to the sodium chloride that requires viscosity and optional conditioner, spices and colouring agent,

(g) in the solution of (f), add acid, alkali or buffer, obtain the pH in 4 to 10 scopes, and

(h) in the solution of (g), add deionized water to 100%.

Embodiment

It below is the conventional method of preparation shampoo of the present invention. The suitable amount of every kind of component is obtained by above description and is obtained by the example formulations shown in the following table.

Adding 1.64%Carbopol 1342 stock solution in container (uses the Quadro disperser to prepare, the function of this disperser is to keep the polymer Uniform Dispersion of powdery and by vacuum powder belt is entered in the current) and deionized water, and be heated to about 70 ℃. Add two kinds of surfactants, namely then sodium laureth sulfate and coconut oil base sodium sarcosinate add blowing agent, coconut monoethanolamide MEA and pearling agent (diglycol stearate), mix until fully dissolving. Then add BHT, stir the mixture until fully dissolving. Make this solution slightly cold, in the well-beaten fungicide component that adds simultaneously. (when adding fungicide, it is acid to help dissolving that pH shows slightly). Next, pyrithione salt is distributed in the mixture, stirs until be uniformly dispersed. Make mixture be cooled to about 40 ℃, under this temperature, add conditioner (polyquaternium-7), anticorrisive agent quaternary ammonium salt-15 and EDTA four sodium, colouring agent and spices, and be used for making the NaCl of solution thickening. The pH of solution is adjusted to 6.9-7.4 with the aqueous solution of 25%NaOH, adds deionized water to final volume. It will be apparent to one skilled in the art that and to use similar method to prepare similar shampoo preparation.

Although above conventional method is gratifying, it has following shortcoming: the stage that is dissolved in the shampoo base-material at ketoconazole is located, and has formed in this technical process with pink color; When pH was adjusted to 6.9-7.4, color may disappear or fade in finished product, but when finished product process stability experiment (at high temperature) under stress, pink color manifests again. To the research of this problem, be surprised to find that and be not only temperature, and the pH scope during solubilization of active ingredient also is crucial; Even slightly acid condition also can cause the formation of some colors. Ketoconazole rate of dissolution under alkali condition is slow, and color forms and enough compromise proposals of the satisfaction between the fast rate of dissolution by obtaining at dissolving ketoconazole under the pH6.9-7.3 scope suppressing. The shampoo that is obtained by Innovative method has several advantages: they no longer need to add the artificial tanning agent; They have the long-time stability of improvement, because they can not change color in time; Just can make first product become limpid, white preparation.

Below be the preparation shampoo, do not need two kinds of Innovative methods of colouring agent.Embodiment A:The pearly-lustre white shampoo (with reference to #780-135) that contains ketoconazole

Component percentage

Purified water 50.72

         Carbopol 1342 NF     0.60

Sodium laureth sulfate 30.00

Coconut oil base sodium sarcosinate 10.00

Coconut monoethanolamide MEA 4.00

Diglycol stearate 1.25

NaOH 0.23

         BHT                  0.10

Ketoconazole 1.00

EDTA four sodium 0.50

Aromatic oil 0.30

Quaternary ammonium salt-15 0.05

Polyquaternium-7 1.00

Sodium chloride0.25

                              100.00

Below narration contains the preparation method of the pearly-lustre white shampoo of ketoconazole: 1. in the container of purified water being packed into, start homogenizer, the Speed Setting of screw at 10rpm, is begun mixing under interior pressure 0.6 bar. 2. the bottom from container adds Carbopol 1342, and pressing in regulating is 0.3 bar, continues to mix 20 minutes with 10rpm. 3. add sodium laureth sulfate and coconut oil base sodium sarcosinate from the bottom of container, begin to be heated to 63 ℃-67 ℃, keep internal pressure in 0.6 bar and propeller speed at 10rpm. 4. stop homogenizer, make container be back to atmospheric pressure, under 10rpm, continue to mix until temperature reaches 63 ℃-67 ℃. 5. under 63 ℃-67 ℃, regulate pressure to 0.6 bar of container, start homogenizer, the Speed Setting of screw continues to mix under 10rpm, adds coconut monoethanolamide MEA. 6. maintain the temperature at 63 ℃-67 ℃, stop homogenizer, under 10rpm, continue to mix until there is not undissolved particle. 7. internal pressure is risen to 0.5 bar, the bottom adding diglycol stearate from container maintains the temperature at 63 ℃-67 ℃, and the Speed Setting of screw continues to mix 5 minutes under 10rpm. 8. the Speed Setting of screw continues to mix under 10rpm, and internal pressure is 0.6 bar, adds NaOH and regulates pH to 7.0-7.3, continues to mix 5 minutes. 9. startup homogenizer, the Speed Setting of screw continue to mix under 10rpm, and internal pressure is 0.6 bar, by suction adding BHT and ketoconazole. 10. maintain the temperature at 63 ℃-67 ℃, the Speed Setting of screw under 10rpm and homogenizer be set under the 1000rpm and continue to mix 40-60 minute, with interval sampling in 15 minutes, by screening and microscopic examination. 11. stop homogenizer, the Speed Setting of screw continues to mix under 10rpm, is cooled to 40 ℃-45 ℃. 12. under 40 ℃-45 ℃, add EDTA four sodium, quaternary ammonium salt-15 and aromatic oil by manhole, only having screw to be set in continuation mixing under the 10rpm, continue cooling. 13. under 25 ℃-30 ℃, add polyquaternium-7 by manhole, screw is set in and continues under the 10rpm to mix. 14. internal pressure is risen to 0.8 bar, adds the pH (if necessary) that hydrochloric acid is adjusted to be needed by suction. 15. make container be back to atmospheric pressure, stop homogenizer, the Speed Setting of screw mixed 10 minutes under 10rpm.

The stability experiment result of three batch samples who contains the pearly-lustre white shampoo of ketoconazole makes under technique slightly changes. Sample is carried out stability experiment.

Reference	Technique change	Color
			#780-134	Under 66 ℃ and pH5.6, add ketoconazole, mixed 80 minutes	Pink
#780-135	Under 66 ℃ and pH7.0, add ketoconazole, mixed 80 minutes	White
			#780-137	Under 40 ℃ and pH7.0, add ketoconazole, mixed 40 minutes	White

Reference	Technique change	The ketoconazole calibrating	Color
				#9601001	Under 67 ℃ and pH5.0, add ketoconazole, mixed 80 minutes.	1.03％	Baby pink
#9601002	Under 67 ℃ and pH7.2, add ketoconazole, mixed 80 minutes.	1.07％	White
				#9601003	Ketoconazole is dissolved in the surfactant system, under 67 ℃, through 80 minutes, adds NaOH, mix 15 minutes (pH=12.5), then add the Carbopol phase.	1.07％	White
#9601004	Ketoconazole is dissolved in the surfactant system, under 67 ℃, through 80 minutes, adds the Carbopol phase, then add immediately NaOH and mixed 40 minutes.	1.05％	White

Embodiment B: the limpid shampoo (with reference to #780-115) that contains ketoconazole

Component percentage

Purified water 42.22

Sodium laureth sulfate 45.00

Coconut oil base sodium sarcosinate 5.00

Coconut monoethanolamide MEA 3.50

         BHT                       0.10

Ketoconazole 1.00

EDTA four sodium 0.50

Aromatic oil 0.30

Quaternary ammonium salt-15 0.05

Polyquaternium-7 1.00

Hydrochloric acid (6N) 0.35

Sodium chloride1.00

                                      100.00

Below narration contains the preparation method of limpid shampoo of ketoconazole: in the container of purified water being packed into, the Speed Setting of screw at 10rpm, is begun mixing under interior pressure 0.6 bar 1.. 2. add sodium laureth sulfate and coconut oil base sodium sarcosinate from the bottom of container, be heated to 63 ℃-67 ℃, keep internal pressure in 0.6 bar and propeller speed at 10rpm. 3. stop homogenizer, make container be back to atmospheric pressure, under 10rpm, continue to mix until temperature reaches 63 ℃-67 ℃. 4. under 63 ℃-67 ℃, regulate pressure to 0.6 bar of container, start homogenizer, the Speed Setting of screw continues to mix under 10rpm, adds coconut monoethanolamide MEA. 6. maintain the temperature at 63 ℃-67 ℃, stop homogenizer, under 10rpm, continue to mix until there is not undissolved particle. 7. startup homogenizer, the Speed Setting of screw continue to mix under 10rpm, and internal pressure is 0.6 bar, by suction adding BHT and ketoconazole. 8. maintain the temperature at 63 ℃-67 ℃, the Speed Setting of screw under 10rpm and homogenizer be set under the 1000rpm and continue to mix 40-60 minute, with interval sampling in 15 minutes, by screening and microscopic examination. 9. stop homogenizer, the Speed Setting of screw continues to mix under 10rpm, is cooled to 40 ℃-45 ℃. 10. under 40 ℃-45 ℃, add EDTA four sodium, quaternary ammonium salt-15 and aromatic oil by manhole, only having screw to be set in continuation mixing under the 10rpm, continue cooling. 11. under 25 ℃-30 ℃, add polyquaternium-7 by manhole, screw is set in and continues under the 10rpm to mix. 12. internal pressure is risen to 0.8 bar, adds the pH (if necessary) that hydrochloric acid is adjusted to be needed by suction. 13. make container be back to atmospheric pressure, stop homogenizer, the Speed Setting of screw mixed 10 minutes under 10rpm.

The stability experiment result of two batch samples who contains the limpid light yellow shampoo of ketoconazole makes under technique change slightly. Sample is carried out stability experiment.

Reference	Technique change	Color
			#780-115	Under 66 ℃ and pH8.2, add ketoconazole, mixed 40 minutes	Limpid is light yellow
#780-138	Under 40 ℃ and pH8.2, add ketoconazole, mixed 40 minutes	Limpid is light yellow

Use the following shampoo preparation of the present invention of general and above-mentioned Innovative method preparation; All quantity hereinafter are weight portions.

Preparation of the present invention is used for the treatment of illness, for example dandruff, seborrhea, control psoriasis, the oil that reduces the scalp generation or sebum and similarly illness and uncomfortable. Said preparation with regular time the interval be applied to the human body affected part, particularly weekly at least one times to every day about 1 time. Preferably in the incipient stage for the treatment of, use more continually them, for example week 4 to 7 times, when obtaining the effect that needs, reduce and frequently use during the late stages of developmet, suppress to have a relapse (for example a week 1 or 2 time).Embodiment 1: the shampoo prescription that is used for normal hair

Component (a) (b)

Sodium laureth sulfate 30 30

Coconut oil base sodium sarcosinate 10 10

Coconut monoethanolamide MEA 44

Ketoconazole USP 0.5 1

Pyrithione salt 0.5 1

Distearyl acid diol ester 1.25 1.25

Polyquaternium-7 11

     Carbopol ^TM1342         0.6    0.6

EDTA four sodium 0.5 0.5

Aromatic oil 0.5 0.5

Sodium chloride 0.3 0.3

25% NaOH 0.92 0.9

Yoshinox BHT 0.1 0.1

Quaternary ammonium salt-15 0.05 0.05

Colouring agent 0.001 0.001

Deionized water is in right amount to 100 100Embodiment 2; The shampoo prescription that is used for oily hair

Component (a) is (c) (b)

Sodium laureth sulfate 33.33 33.33 33.33

Coconut oil base sodium sarcosinate 11 11 11

Coconut monoethanolamide MEA 444

Ketoconazole USP 0.5 0.75 1.2

Pyrithione salt 0.5 0.25 0.8

Distearyl acid diol ester 1.25 1.25 1.25

Polyquaternium-7 0.6 0.6 0.6

  Carbopol ^TM1342        0.75    0.75    0.75

EDTA four sodium 0.5 0.5 0.5

Aromatic oil 0.5 0.5 0.5

Sodium chloride 0.3 0.3 0.3

25% NaOH 1.18 1.243 1.18

Yoshinox BHT 0.1 0.1 0.1

Quaternary ammonium salt-15 0.05 0.05 0.05

Colouring agent 0.0053 0.0053 0.0053

Deionized water is in right amount to 100 100 100Embodiment 3: the shampoo prescription that is used for dryness or damaged hair

Component (a) is (c) (b)

Sodium laureth sulfate 30 30 30

Coconut oil base sodium sarcosinate 10 10 10

Coconut monoethanolamide MEA 444

Ketoconazole USP 0.75 0.33 1

Pyrithione salt 0.25 0.67 1

Distearyl acid diol ester 1.25 1.25 1.25

Polyquaternium-7 555

  Carbopol ^TM1342        0.5     0.5     0.5

EDTA four sodium 0.5 0.5 0.5

Aromatic oil 0.5 0.5 0.5

Sodium chloride 0.4 0.4 0.3

25% NaOH 0.7333 0.7333 1.19

Yoshinox BHT 0.1 0.1 0.1

Quaternary ammonium salt-15 0.05 0.05 0.05

Colouring agent 0.0018 0.0018 0.0018

Deionized water is in right amount to 100 100 100

In the prescription that embodiment 1-3 provides more than all, the ratio of NaOH can slightly change, and reaches preferred pH value at 6.9-7.4, and the variable-scale of salt (NaCl) reaches the viscosity that needs. Prescription according to the Innovative method preparation has the canescence pearlescent appearance, has wherein omitted colouring agent.Embodiment 4: the mixture of pyrithione zinc and ketoconazole (with reference to #822-076)

Component percentage

Purified water 44.30

Sodium laureth sulfate 15.00

NaLS 10.00

Lauryl sulfate TEA 12.00

Pyridone sulphur cave zinc (48%) 2.10

Ketoconazole 1.00

Methylparoban 0.20

Oxybenzene propyl formate 0.05

Coconut monoethanolamide MEA 5.00

Diglycol stearate 1.25

Polyquaternium-7 3.00

Imidazolidinyl urea 0.50

AMPHORAM C30 5.00

Citric acid 0.35

Spices 0.25

                               100.00 Embodiment 5: the mixture of pyrithione zinc and Elubiol (with reference to #822-075)

Component percentage

Purified water 44.30

Sodium laureth sulfate 15.00

NaLS 10.00

Lauryl sulfate TEA 12.00

Pyridone sulphur cave zinc (48%) 2.10

         Elubiol               1.00

Methylparoban 0.20

Oxybenzene propyl formate 0.05

Coconut monoethanolamide MEA 5.00

Diglycol stearate 1.25

Polyquaternium-7 3.00

Imidazolidinyl urea 0.50

AMPHORAM C30 5.00

Citric acid 0.35

Spices 0.25

                              100.00

In above embodiment 4 and 5 prescriptions that provide, the ratio of citric acid can slightly change, and reaches preferred pH value at 6.9-7.4, and this prescription is according to the Innovative method preparation, has the white pearlescent outward appearance.

Embodiment 6: the minimum inhibitory concentration of the shampoo of anti-ovum pityrosporum ovale and Candida albicans

Use the shampoo of embodiment 4 and 5, shampoo base-material and every kind of two kinds of a kind of shampoo base-materials that only contain in two kinds of active components of lacking active component are tested the external activity experiment of five kinds of bacterial strains and a kind of Candida albicans H29 bacterial strain of their anti-ovum pityrosporum ovale ATCC numberings 42132,44337,44340,44342 and 44343. Adding Tween 80 (2ml/l) and glyceryl monostearate (2.5g/l) directly is diluted to shampoo in the culture medium, obtain the shampoo of 0.1%-40% concentration in culture medium, this culture medium is to differentiate sensitivity experiments agar medium (DST; Oxoid, UK). Thereby minimum inhibitory concentration (MIC) value is for overall shampoo, and not just to active component. MIC is the least concentration of observing total shampoo that suppresses of growing. Microorganism is with 10⁷Cells/ml (ovum pityrosporum ovale) and 10⁶Cells/ml (Candida albicans) concentration adds in the agar medium. Test panel is at 37 ℃ of lower insulations, reading after 1,2 and 3 day. All shampoos are tested in duplicate.

The shampoo that contains the embodiment 4 of 1% ketoconazole and 1% pyrithione zinc (ZPT)

	Ovum pityrosporum ovale ATCC42132	Ovum pityrosporum ovale ATCC44337	Ovum pityrosporum ovale ATCC44340	Ovum pityrosporum ovale ATCC44342	Ovum pityrosporum ovale ATCC44343	Candida albicans H.29
							The shampoo base-material	5.0％	5.0％	5.0％	5.0％	5.0％	5.0％
Base-material+1% ketoconazole	0.5％	0.5％	0.5％	0.5％	0.5％	0.5％
							Base-material+1% ZPT	2.5％	2.5％	2.5％	2.5％	2.5％	5.0％
Base-material+1% ketoconazole+1 %ZPT	0.1％	0.1％	0.1％	0.1％	0.1％	0.1％

The base-material that contains 1% ketoconazole+1%ZPT is Duoed 5 times than the base-material that contains 1% ketoconazole or the base-material validity that contains 1% ZPT, and synergy has been described.

The shampoo that contains the embodiment 5 of 1%Elubiol and 1% pyrithione zinc (ZPT)

	Ovum pityrosporum ovale ATCC42132	Ovum pityrosporum ovale ATCC44337	Ovum pityrosporum ovale ATCC44340	Ovum pityrosporum ovale ATCC44342	Ovum pityrosporum ovale ATCC44343	Candida albicans H.29
							The shampoo base-material	5.0％	5.0％	5.0％	5.0％	10.0％	20.0％
Base-material+1% Elubiol	1.0％	1.0％	1.0％	1.0％	1.0％	5.0％
							Base-material+1% ZPT	2.5％	2.5％	2.5％	2.5％	2.5％	5.0％
Base-material+1% ketoconazole+1 %ZPT	0.1％	0.1％	0.1％	0.1％	0.1％	0.1％

The base-material that contains 1%Elubiol+1%ZPT is Duoed 10 times than the base-material that contains 1%Elubiol or the base-material validity that contains 1 %ZPT, and synergy has been described.

Claims (12)

1. a body and function or hair cleaning combination, it comprises:

(a-1) ketoconazole or according to the Shandong than Ou Zuowei the first active component,

(a-2) pyrithione salt is as the second active component, and

(b) the known body and function of prior art or hair cleaning products component be as carrier,

Wherein first and second kinds of active components are to exist so that the growth that suppresses dermatophyte is produced mutual synergistic amount.

2. according to claim 1 composition, wherein pyrithione salt is pyrithione zinc or sodium pyrithione.

3. according to claim 1 and 2 composition, wherein the content of the first active component is to about 2% (w/w) scope about 0.1%, the content of the second active component is about 0.05% to about 2% (w/w) scope, and the latter's amount is that the weight by pyrithione zinc represents.

4. shampoo, it is formulated by each composition among the claim 1-3.

5. according to claim 4 shampoo, wherein the known shampoo component of prior art comprise one or more surfactants, blowing agent, be enough to make final preparation viscosity at room temperature at thickener, anticorrisive agent, the antioxidant of 4000 to 9000mPa.s scopes, be enough to make the pH of shampoo at acid or alkali or the buffer of about 4 to 10 scopes.

6. according to claim 5 shampoo, it comprises one or more surfactants, is selected from C_14-16Alkene sulfonic acid sodium, NaLS, sodium laureth sulfate, coconut acylamino-propyl group amine oxide, lauryl amine oxide, the amino DEA of lauroyl, AMPHORAM C30, Empigen, coco dimethyl sulfopropyl betaine, cocoyl sodium sarcosinate, Disodium Monooleamido MIPA-Sulfosuccinate, DISODIUM COCO AMIDOMIPA SULFOSUCCINATE, lauryl ether disodium sulfosuccinate, coconut both sexes carboxyl-glycinate, the amino MEA disodium sulfosuccinate of oleoyl, amine glycinate, amine propionate and amine sulfobetaines and their mixture.

7. according to claim 5 shampoo, wherein blowing agent is selected from aliphatic acid list and di alkanolamide, comprises coconut monoethanolamide MEA, coconut monoethanolamide DEA, oleamide MEA, oleamide DEA and their mixture.

8. according to claim 5 shampoo, wherein antioxidant is that consumption is about 0.01% Yoshinox BHT or butylated hydroxyanisol to about 1% (w/w).

9. according to claim 5 shampoo, it also comprises conditioner.

10. according to claim 5 shampoo, it also comprises one or more pearling agents, and it is selected from diglycol stearate, Tego-stearate and their mixture.

11. shampoo according to claim 5, it also comprises one or more spices and one or more colouring agents.

12. the method for the shampoo of each definition among a composition for preparing each definition among the claim 1-3 or the claim 4-11 may further comprise the steps:

(a) solution of heating thickener and deionized water,

(b) surfactant, blowing agent and optional pearling agent are mixed with solution (a),

(c) BHT is mixed with solution (b),

(d) fungicide is mixed with solution (c),

(e) pyrithione salt is dispersed in the mixture of (d),

(f) make the slightly cooling of suspension of (e), with them with anticorrisive agent, mix for being thickened to the sodium chloride that requires viscosity and optional conditioner, spices and colouring agent,

(g) in the solution of (f), add acid, alkali or buffer, obtain the pH in 4 to 10 scopes, and

(h) in the solution of (g), add deionized water to 100%.